Aqueous humor metabolomic profiling identifies a distinct signature in pseudoexfoliation syndrome
PurposePEXS was first described in 1917, yet its etiology still needs clarification. An imbalance between oxidants and antioxidants plays a significant role. PEXS leads to various ocular complications, including increased risk during cataract surgery due to weak zonules, lens dislocation, and reduce...
Saved in:
| Main Authors: | , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Frontiers Media S.A.
2025-01-01
|
| Series: | Frontiers in Molecular Biosciences |
| Subjects: | |
| Online Access: | https://www.frontiersin.org/articles/10.3389/fmolb.2024.1487115/full |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1832591019272568832 |
|---|---|
| author | Arturs Zemitis Arturs Zemitis Juris Vanags Juris Vanags Theresa Schiemer Theresa Schiemer Kristaps Klavins Kristaps Klavins Guna Laganovska Guna Laganovska |
| author_facet | Arturs Zemitis Arturs Zemitis Juris Vanags Juris Vanags Theresa Schiemer Theresa Schiemer Kristaps Klavins Kristaps Klavins Guna Laganovska Guna Laganovska |
| author_sort | Arturs Zemitis |
| collection | DOAJ |
| description | PurposePEXS was first described in 1917, yet its etiology still needs clarification. An imbalance between oxidants and antioxidants plays a significant role. PEXS leads to various ocular complications, including increased risk during cataract surgery due to weak zonules, lens dislocation, and reduced visual outcomes. Our study investigates whether metabolomics can provide insights into this ocular pathology.MethodsThe study included 183 patients undergoing cataract surgery at Pauls Stradins Clinical University Hospital. 104 patients did not have PEXS, while 79 were diagnosed with the condition. Intraocular fluid samples from these patients were analyzed using targeted metabolite analysis, performed through HILIC liquid chromatography coupled with mass spectrometry detection.ResultsThe aqueous humor of PEXS patients contains statistically significant higher levels of cystine (p < 0.001), citrulline (p < 0.001), phenylalanine (p = 0.041), tyrosine (p = 0.025), serine (p = 0.030), arginine (p = 0.017), lactic acid (p = 0.055), tryptophan (p = 0.055), and creatinine (p = 0.022). These results suggest a potential link to ferroptosis.ConclusionFerroptosis is a form of programmed cell death characterized by iron-dependent LPO. The inhibition of the antiporter system Xc− leads to increased oxidative stress, suggesting that the changes seen in PEXS could be linked to ferroptosis. Our findings indicate that cysteine synthesis occurs via the transsulfation pathway, attributable to inhibiting the antiporter system Xc−. Treatment of pseudoexfoliation should lower the oxidative stress inside the anterior chamber by reducing the uptake of PUFAs, lower iron levels, and cysteine supplementation. |
| format | Article |
| id | doaj-art-313316b4ad224353b5191e4d06bb89ed |
| institution | Kabale University |
| issn | 2296-889X |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Molecular Biosciences |
| spelling | doaj-art-313316b4ad224353b5191e4d06bb89ed2025-01-23T05:10:20ZengFrontiers Media S.A.Frontiers in Molecular Biosciences2296-889X2025-01-011110.3389/fmolb.2024.14871151487115Aqueous humor metabolomic profiling identifies a distinct signature in pseudoexfoliation syndromeArturs Zemitis0Arturs Zemitis1Juris Vanags2Juris Vanags3Theresa Schiemer4Theresa Schiemer5Kristaps Klavins6Kristaps Klavins7Guna Laganovska8Guna Laganovska9Department of Ophthalmology, Riga Stradins University, Riga, LatviaPauls Stradins Clinical University Hospital, Clinic of Ophthalmology, Riga, LatviaDepartment of Ophthalmology, Riga Stradins University, Riga, LatviaPauls Stradins Clinical University Hospital, Clinic of Ophthalmology, Riga, LatviaInstitute of Biomaterials and Bioengineering, Faculty of Natural Sciences and Technology, Riga Technical University, Riga, LatviaBaltic Biomaterials Centre of Excellence, Headquarters at Riga Technical University, Riga, LatviaInstitute of Biomaterials and Bioengineering, Faculty of Natural Sciences and Technology, Riga Technical University, Riga, LatviaBaltic Biomaterials Centre of Excellence, Headquarters at Riga Technical University, Riga, LatviaDepartment of Ophthalmology, Riga Stradins University, Riga, LatviaPauls Stradins Clinical University Hospital, Clinic of Ophthalmology, Riga, LatviaPurposePEXS was first described in 1917, yet its etiology still needs clarification. An imbalance between oxidants and antioxidants plays a significant role. PEXS leads to various ocular complications, including increased risk during cataract surgery due to weak zonules, lens dislocation, and reduced visual outcomes. Our study investigates whether metabolomics can provide insights into this ocular pathology.MethodsThe study included 183 patients undergoing cataract surgery at Pauls Stradins Clinical University Hospital. 104 patients did not have PEXS, while 79 were diagnosed with the condition. Intraocular fluid samples from these patients were analyzed using targeted metabolite analysis, performed through HILIC liquid chromatography coupled with mass spectrometry detection.ResultsThe aqueous humor of PEXS patients contains statistically significant higher levels of cystine (p < 0.001), citrulline (p < 0.001), phenylalanine (p = 0.041), tyrosine (p = 0.025), serine (p = 0.030), arginine (p = 0.017), lactic acid (p = 0.055), tryptophan (p = 0.055), and creatinine (p = 0.022). These results suggest a potential link to ferroptosis.ConclusionFerroptosis is a form of programmed cell death characterized by iron-dependent LPO. The inhibition of the antiporter system Xc− leads to increased oxidative stress, suggesting that the changes seen in PEXS could be linked to ferroptosis. Our findings indicate that cysteine synthesis occurs via the transsulfation pathway, attributable to inhibiting the antiporter system Xc−. Treatment of pseudoexfoliation should lower the oxidative stress inside the anterior chamber by reducing the uptake of PUFAs, lower iron levels, and cysteine supplementation.https://www.frontiersin.org/articles/10.3389/fmolb.2024.1487115/fullpseudoexfoliation syndromecysteineantiporter system Xc−argininetryptophanoxidative stress |
| spellingShingle | Arturs Zemitis Arturs Zemitis Juris Vanags Juris Vanags Theresa Schiemer Theresa Schiemer Kristaps Klavins Kristaps Klavins Guna Laganovska Guna Laganovska Aqueous humor metabolomic profiling identifies a distinct signature in pseudoexfoliation syndrome Frontiers in Molecular Biosciences pseudoexfoliation syndrome cysteine antiporter system Xc− arginine tryptophan oxidative stress |
| title | Aqueous humor metabolomic profiling identifies a distinct signature in pseudoexfoliation syndrome |
| title_full | Aqueous humor metabolomic profiling identifies a distinct signature in pseudoexfoliation syndrome |
| title_fullStr | Aqueous humor metabolomic profiling identifies a distinct signature in pseudoexfoliation syndrome |
| title_full_unstemmed | Aqueous humor metabolomic profiling identifies a distinct signature in pseudoexfoliation syndrome |
| title_short | Aqueous humor metabolomic profiling identifies a distinct signature in pseudoexfoliation syndrome |
| title_sort | aqueous humor metabolomic profiling identifies a distinct signature in pseudoexfoliation syndrome |
| topic | pseudoexfoliation syndrome cysteine antiporter system Xc− arginine tryptophan oxidative stress |
| url | https://www.frontiersin.org/articles/10.3389/fmolb.2024.1487115/full |
| work_keys_str_mv | AT arturszemitis aqueoushumormetabolomicprofilingidentifiesadistinctsignatureinpseudoexfoliationsyndrome AT arturszemitis aqueoushumormetabolomicprofilingidentifiesadistinctsignatureinpseudoexfoliationsyndrome AT jurisvanags aqueoushumormetabolomicprofilingidentifiesadistinctsignatureinpseudoexfoliationsyndrome AT jurisvanags aqueoushumormetabolomicprofilingidentifiesadistinctsignatureinpseudoexfoliationsyndrome AT theresaschiemer aqueoushumormetabolomicprofilingidentifiesadistinctsignatureinpseudoexfoliationsyndrome AT theresaschiemer aqueoushumormetabolomicprofilingidentifiesadistinctsignatureinpseudoexfoliationsyndrome AT kristapsklavins aqueoushumormetabolomicprofilingidentifiesadistinctsignatureinpseudoexfoliationsyndrome AT kristapsklavins aqueoushumormetabolomicprofilingidentifiesadistinctsignatureinpseudoexfoliationsyndrome AT gunalaganovska aqueoushumormetabolomicprofilingidentifiesadistinctsignatureinpseudoexfoliationsyndrome AT gunalaganovska aqueoushumormetabolomicprofilingidentifiesadistinctsignatureinpseudoexfoliationsyndrome |